Pain-Related Post-Exertional Malaise in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia: A Systematic Review and Three-Level Meta-Analysis

Abstract

Objective Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are two debilitating, moderately comorbid illnesses in which chronic musculoskeletal pain symptoms are prevalent. These individuals can experience post-exertional malaise (PEM), a phenomenon where symptom severity is worsened 24hr or longer following physical stress, but the pain-related component of PEM is not well characterized. Design Systematic review and meta-analysis Methods Case-control studies involving adults with ME/CFS or FM and measuring pain symptoms before and after exposure to a standardized aerobic exercise test were included. Hedges’ d effect sizes were aggregated using random effects models and potential moderators were explored with meta-regression analysis. Results were adjusted for nesting effects using three-level modeling. Results Forty-five effects were extracted from 15 studies involving 306 patients and 292 healthy controls. After adjusting for nesting effects, we observed a small-to-moderate effect indicating higher post-exercise pain in patients than controls (Hedges’ d=0.42; 95% CI: 0.16, 0.67). The mean effect was significantly moderated by pain measurement timepoint (b = -0.19, z = -2.57, P = 0.01) such that studies measuring pain 8-72hr post-exercise showed larger effects (d = 0.71, 95% CI = 0.28-1.14) than those measuring pain 0-2hr post-exercise (d = 0.32, 95% CI = 0.10-0.53). Conclusions People with ME/CFS and FM experience small-to-moderate increases in pain severity following exercise which confirms pain as a component of PEM and emphasizes its debilitating impact in ME/CFS and FM. Future directions include determining mechanisms of pain-related PEM and developing exercise prescriptions that minimize symptom exacerbation in these illnesses.

Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study

“…When considering physical activity for people with ME/CFS, clinicians face the challenge of helping patients avoid the negative effects of acute exercise (e.g., symptom exacerbation) [71,72], while moving them towards experiencing the health benefits associated with a more physically active lifestyle [73]. A logical approach is to develop exercise prescriptions which strike a balance between minimizing symptom exacerbation and maximizing function, however, there is limited information on the intensity threshold at which this ideal balance occurs or guidance on how to establish this threshold for individual patients.…”

Fibromyalgia and Chronic Fatigue Syndromes: A systematic review and meta-analysis of cardiorespiratory fitness and neuromuscular function compared with healthy individuals

“…This concept of heightened afferent feedback could contribute not only to generalized and exercise-related fatigue but also to the relative muscular weakness of patients [ 14 ]. It may also contribute to heightened rates of perceived exertion and pain during exercise reported by patients [ 25 , 46 ].…”

“…Our primary approach was to combine results of patients with CFS and FMS for comparison to healthy controls, given the overlap that is present between the two syndromes [43][44][45] and the small sample sizes. This approach was also implemented in a previous systematic review with meta-analysis [46]. However, we have also provided a subgroup analysis differentiating studies from FMS and CFS for each available outcome measurement (Figs 3 and 4 and S3 File).…”

Male vs. Female Differences in Responding to Oxygen–Ozone Autohemotherapy (O2-O3-AHT) in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

“…Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex pathology, and was recently reviewed in [ 1 ]. ME/CFS must be considered a serious and long-term syndrome, which is characterized by fatigue and debilitating muscular–skeletal pain, conditions that affect many fundamental aspects of people’s social habits [ 2 , 3 , 4 ]. Fatigue is a major symptom in ME/CFS and its treatment is accounted for in many forerunners in Italy [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”